Pulmonary tuberculosis in Kumasi, Ghana: presentation, drug resistance, molecular epidemiology and outcome of treatment.

To assist implementation of tuberculosis (TB) control measures, knowledge of the disease characteristics in a community is essential. This study in Kumasi, Ghana, correlates the clinical presentation, microbiology, molecular epidemiology and clinical outcome of thirty consecutively diagnosed patients with new smear-positive pulmonary TB. Several important factors that potentially promote disease transmission in the community were identified: patients had prolonged duration of productive cough prior to diagnosis (mean=4.1 months; SD=2.1); the disease was typically advanced at presentation and Ziehl-Neelson sputum smears indicated a high bacterial load (80% graded > AFB++); home accommodation was overcrowded with a mean of 3.3 other persons sleeping in the same room as the patients at night. IS6110 restriction fragment length polymorphism (RFLP) fingerprinting of 25 isolated (23 Mycobacterium tuberculosis and 2 Mycobacterium africanum) from epidemiologically unrelated cases identified 3 identical strains and 3 clusters containing 2, 4 and 8 isolates of > or =80% similarity, suggesting high rates of disease transmission. A high prevalence of primary resistance to isoniazid was found (6 out 26; 23%) but resistance to rifampicin, pyrazinamide, ethambutol, streptomycin and ciprofloxacin was not detected. Smear coversion at 2 months and final outcome of treatment with short courses chemotherapy were independent of isoniazid resistance, but the rate of treatment default was unacceptably high (37%). High rates of disease transmission, primary isoniazid resistance and treatment default all indicate poor TB control. The use of rifampicin-containing short-course chemotherapy in this community must be accompanied by adequate resources and infrastructure to ensure very stringent treatment supervision to improve case-holding and reduce the risk of multi-drug resistance.

Isolation of environmental mycobacteria from clinical specimens in south-east England: 1973-1993.

SETTING: A reference centre for tuberculosis bacteriology serving South-East England. OBJECTIVE: The number of cultures of environmental mycobacteria (EM) submitted to regional and reference laboratories in the UK is increasing, and is adding considerably to the workload of these laboratories. The changing trends in the numbers and nature of EM submitted to the Dulwich Public Health Laboratory Regional Tuberculosis Centre (RTC), have been analysed to establish the nature of the increase. DESIGN: This study is based on all cultures of EM submitted to RTC between 1973 and 1993. The cultures were grouped according to year of first isolation, number of isolates and data supplied by the client laboratories, including age and human immunodeficiency virus (HIV) status of the patients and the anatomical sites from which the mycobacteria were isolated. RESULTS: A total of 9379 EM from 6668 patients was received. Single and multiple isolates were received, respectively, from 4681 and 1192 patients not known to be HIV positive and from 477 and 318 who were known to be HIV positive. The annual number of patients not known to be HIV positive with isolates of probable clinical significance increased steadily from less than 40 in 1973 to over 100 per year since 1990. Isolates of doubtful clinical significance also showed an increase over time. The annual numbers from HIV positive patients increased steeply following the first such isolates in 1984. CONCLUSIONS: The data show that the annual number of isolates of EM from both HIV positive and negative patients is increasing both absolutely and relatively to isolates of Mycobacterium tuberculosis. This trend should be considered when planning the future scope and activities of mycobacterium reference laboratories, including the introduction of new DNA-based diagnostic methods.

Follow up of an immunocompromised contact group of a case of open pulmonary tuberculosis on a renal unit.

BACKGROUND: The organisation, management, outcome and cost of follow up of a large group of mainly immunocompromised patients and healthcare workers who were exposed to a staff member of a London renal unit with smear positive pulmonary tuberculosis are described. METHODS: Following British Thoracic Society (BTS) guidelines, 576 close contacts were identified and divided into three groups: (1) 303 renal patients including 61 with renal transplants; (2) 90 surgical patients; and (3) 183 staff members. Screened contacts were interviewed, completed a symptoms questionnaire, and were offered a chest radiograph and Heaf or Mantoux test if appropriate with referral to a chest physician if required. RESULTS: Overall, 524 (85%) living contacts have been screened: 243 (97%) renal (first screening), 63 (70%) surgical, and 135 (74%) staff contacts. Thirty one transplant patients were prescribed isoniazid chemoprophylaxis. Fifty two renal patients had died before screening and 11 deaths occurred after first interview. One case of tuberculosis epidemiologically related to the index case was diagnosed on clinical criteria. A review of the case records and/or death certificates and entries on to tuberculosis registers indicated no further cases. The cost of the investigation was estimated to be approximately franc25 000, or franc44 per contact screened, with staff costs comprising 79% of the total. CONCLUSIONS: Undiagnosed tuberculosis in healthcare workers working with immunosuppressed patients can lead to large and expensive follow up studies. The applicability of the 1990 and 1994 BTS guidelines to the investigation of tuberculosis in an immunocompromised nosocomial group, and the role of the infection control doctor and the consultant in Communicable Disease Control in overlapping nosocomial and community incidents, are discussed.

Tuberculosis and AIDS.

Since the mid-1980s, the rate of decline in reported cases of tuberculosis (TB) has reached a plateau or reversed because of a combination of poverty and increased homelessness, immigration and displacement, poorly managed and supplied TB control programmes and, particularly in the developing world, the emergence of human immunodeficiency virus (HIV) infection. TB in HIV-positive patients may present atypically, both clinically and radiologically, with a lower probability of sputum positivity, greater difficulty in diagnosis, and a more rapid clinical deterioration than TB in HIV-seronegative patients. The emergence of multiple-drug-resistant strains of Mycobacterium tuberculosis, particularly in patients infected by HIV, carries a high mortality and has been associated with outbreaks in Europe and the USA. Microscopy and culture form the basis of diagnosis, but there is a need for more rapid diagnostic techniques and novel methods of drug susceptibility testing. Prolonged supervised treatment programmes and the development of new chemotherapeutic agents and regimens are essential prerequisites for successful TB therapy in AIDS patients. This review examines the clinical, microbiological and epidemiological issues associated with TB in HIV-infected individuals.

Restriction fragment length polymorphism analysis rules out cross-infection among renal patients with tuberculosis.

A cluster of five cases of tuberculosis occurred on a renal unit in 1993. The initial impression was that this was an outbreak, and cross-infection was suspected. Restriction fragment length polymorphism analysis was carried out on the strains of Mycobacterium tuberculosis isolated from these cases, using a DNA probe directed against the insertion sequence IS6110. DNA fingerprints obtained by this method differed for all the strains tested, ruling out cross-infection as a cause of the outbreak. This technique is a useful adjunct to standard epidemiological investigations in outbreaks of tuberculosis.

Molecular biology in the diagnosis and epidemiology of tuberculosis.

Tuberculosis is the predominant infectious cause of mortality today, killing 3 million people annually. The cornerstones of diagnosis rest on microscopy of specimens using auramine and Ziehl-Neelsen stains followed by culture on Lowenstein-Jensen or alternative media. The long generation time of Mycobacterium tuberculosis means 2-8 weeks usually elapse before a result is available to the clinician. This has stimulated research into the use of molecular diagnostic techniques. This article reviews the use and limitations of DNA hybridization, restriction fragment length polymorphism, pulsed-field gel electrophoresis and the polymerase chain reaction in the diagnosis and epidemiology of tuberculosis. The applicability of molecular biology to determine drug resistance is also addressed.

Audit of bronchoscope disinfection: a survey of procedures in England and Wales and incidents of mycobacterial contamination.

Procedures used for cleaning/disinfection of fibreoptic bronchoscopes and incidents of mycobacterial contamination were assessed by postal questionnaire. Information supplied by the Infection Control Doctor in 129 of 198 hospitals (65.2%) was used to audit local practice for compliance with national guidelines. Discrepancies between recommended and local practice included lack of specification of detergent/cleaning agent (57%), inadequate contact time for chemical disinfection (40%) and the use of tap water rather than sterile water for rinsing the disinfected bronchoscope (39.7%). Other procedural anomalies associated with mycobacterial contamination included failure to adhere to manufacturers' instructions to dismantle valves prior to cleaning and to autoclave valves/accessories. The association of mycobacterial incidents with the use of automatic washer/disinfectors (17 of 18 incidents) together with Department of Health warnings of build-up of biofilm within these chemical-process machines gives further cause for concern.